Anti-ulcer properties have been reported for a number of compounds having the oleanane-type of triterpenoid structure. Amongst these compounds glycyrrhetinic acid(1)(3.beta.-hydroxy-11-oxo-18.beta.-olean-12-en-30-oic acid) esters, amides and salts thereof are particularly known for their usefull anti-ulcer activities and some of these compounds have also been used in the treatment of ulcers. One specific derivative of glycyrrhetinic acid that received widespread attention is carbenoxolone sodium (U.S. Pat. No. 3,070,623) which is the disodium salt of the hemisuccinate of glycyrrhetinic acid. It is reported to prevent the formation and to effect the healing of gastric ulcers in animals and humans. U.S. Pat. Nos. 3,766,206, 3,934,027 and 3,859,328 report 18.beta.-glycyrrhetinic acid amides to be effective for the treatment of and for prevention of gastric and duodenal ulcers when administrered orally or intraperitoneally. In Belgian Pat. No. 628,444 the anti-ulcer properties of a number of metal salts of glycyrrhetinic acid and its hemi-esters are reported. In European Pat. No. 0,009,801 (18.beta. and 18.alpha.)-2.alpha.-cyano-3,11-dioxo-olean-12-en-29-oic acid and lower alkyl derivatives thereof are reported to be effective in the treatment and/or prevention of gastric and duodenal ulcers when administered orally.
Glycyrrhizinic acid, the .beta.,.beta.'-glucoronic acid ester of glycyrrhetinic acid, is present in liquorice, which is known to be effective in the treatment of gastric and duodenal ulcers. In British Pat. No. 1,445,831 it is claimed that the aluminium or iron salts of glycyrrhizinic acid are effective anti-ulcer compounds with hardly any or none of the undesirable side effects known for the parent acid.
Derivatives of ursolic acid are also known to possess anti-ulcer properties. In British Pat. No. 1,251,977, for instance, the preparation and anti-ulcer properties of esters of ursolic acid of the type 2 (R and R' not equal to hydrogen) are described.
In British Pat. No. 1,205,012 the isolation of liquiritic acid (3) from and extract of Glycyrrhiza glabra is described. Liquiritic acid, which is a stereo-isomer of glycyrrhetinic acid (1), has been found to possess cicatrisant, anti-inflammatory and anti-ulcer properties.
Derivatives of oleanolic acid (oleanolic acid: 4, R and R'=H) have also been acclaimed for their anti-ulcer properties. In British Pat. No. 1,251,976 esters of the type 4 ##STR1##
(with R and R' not equal to hydrogen) of oleanolic acid are reported to be active anti-ulcer compounds. In Example 10 of the latter patent the glucose induced anti-ulcer activity of three of the esters and oleanolic acid are given. Oleanolic acid was included in this test apparently for purposes of reference or comparison.
While the three esters showed marked reduction (21 to 60%) in ulceration, a non-significant reduction of 8% in ulceration was observed for oleanolic acid. This test suggests that the chemically induced ulceration is not significantly reduced by oral administration of oleanolic acid. In another report the anti-ulcer activities of glycyrrhetinic acid and related compounds, including oleanolic acid, were evaluated (S. Shibata in Proc. Asian Symp. Med. Plants Spices, K. Kusamran (Ed), vol. 1, pp. 59-78, 1981). Firstly, the inhibiting activities against stress-induced ulceration in mice are given (p. 65). Two of the test compounds (glycyrrhetinic acid and olean-12-en-3.beta., 30-diol) were reported to exhibit promising inhibiting activity. By contrast, the results obtained in the latter test suggest non-significant, if any, inhibiting activity against stress-induced ulceration for oleanolic acid. The paper also describes (p. 66) the effect of the glycyrrhetinic acid type of compounds against aspirin-induced ulceration, but only two compounds (glycyrrhetinic acid and olean-12-en-3.beta., 30-diol) which showed positive reduction of the stress-induced ulceration, were included.
It is therefore seen that although oleanolic acid has been included in tests together with other oleanane-type of triterpenoid compounds, the results reported showed no substantial, if any, preventative effect for oleanolic acid against stress-induced and chemically-induced ulceration.
The inescapable conclusion from the prior art data is therefore that oleanolic acid is not suitable for the prevention of stress-induced and chemically-induced ulceration. Furthermore, no mention can be found in the prior apt of any healing effects of oleanolic acid in respect of ulcers.